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US4530792A - Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate - Google Patents

Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate Download PDF

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Publication number
US4530792A
US4530792A US06/438,228 US43822882A US4530792A US 4530792 A US4530792 A US 4530792A US 43822882 A US43822882 A US 43822882A US 4530792 A US4530792 A US 4530792A
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US
United States
Prior art keywords
dioxopenicillanoyloxymethyl
formula
mixture
added
imino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US06/438,228
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English (en)
Inventor
Paul D. Weeks
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pfizer Corp SRL
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Pfizer Corp SRL
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pfizer Corp SRL filed Critical Pfizer Corp SRL
Priority to US06/438,228 priority Critical patent/US4530792A/en
Assigned to PFIZER INC. reassignment PFIZER INC. ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: WEEKS, PAUL D.
Priority to PH29750A priority patent/PH19573A/en
Priority to EP83306460A priority patent/EP0108545B1/en
Priority to AT83306460T priority patent/ATE24322T1/de
Priority to DE8383306460T priority patent/DE3368417D1/de
Priority to CS838030A priority patent/CS235986B2/cs
Priority to IE2539/83A priority patent/IE56179B1/en
Priority to FI833961A priority patent/FI76576C/fi
Priority to GT198303898A priority patent/GT198303898A/es
Priority to PL1983244352A priority patent/PL142735B1/pl
Priority to CA000440002A priority patent/CA1204736A/en
Priority to PT77580A priority patent/PT77580B/pt
Priority to YU2162/83A priority patent/YU43989B/xx
Priority to DD83256136A priority patent/DD213926A5/de
Priority to NZ206108A priority patent/NZ206108A/en
Priority to ES526942A priority patent/ES526942A0/es
Priority to AU20821/83A priority patent/AU541962B2/en
Priority to HU833735A priority patent/HU189769B/hu
Priority to DK497483A priority patent/DK163515C/da
Priority to GR72828A priority patent/GR78943B/el
Priority to ZA838091A priority patent/ZA838091B/xx
Priority to IL70095A priority patent/IL70095A/xx
Priority to KR1019830005159A priority patent/KR860001494B1/ko
Priority to EG681/83A priority patent/EG15987A/xx
Priority to JP58205706A priority patent/JPS5998090A/ja
Publication of US4530792A publication Critical patent/US4530792A/en
Application granted granted Critical
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
    • C07D499/28—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with modified 2-carboxyl group
    • C07D499/32—Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring

Definitions

  • the invention relates to a process for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate by deacylation of a compound of the formula ##STR1## and to intermediate imino chlorides and imino (C 1 -C 4 )-alkyl ethers.
  • Penicillanic acid 1,1-dioxide is known from U.S. Pat. No. 4,234,579 to be an effective beta-lactamase inhibitor and antibacterial agent.
  • U.S. Pat. No. 4,244,951 and U.S. Pat. No. 4,342,772 disclose bis esters of the formula ##STR2## wherein R a is H or certain acyl groups of known antibacterial agents.
  • R a can represent 2-phenylacetyl, 2-phenoxyacetyl, D-2-amino-2-phenylacetyl or D-2-amino-2-(p-hydroxyphenyl)acetyl.
  • the latter compound is prepared by coupling the appropriate derivatives of penicillanic acid 1,1-dioxide and 6-protected-aminopenicillanic acid and removal of protecting group from the coupled product of formula (V) where R a is an amino-protecting group, e.g. benzyloxycarbonyl.
  • U.S. Pat. No. 3,896,110 discloses a process for preparation of 6-aminopenicillanic acid by reacting a natural penicillin such as Penicillin G or Penicillin V with a phosphorus halide to protect the carboxyl group, reacting this with an acid halide to form the corresponding penicillin imino halide, reacting the imino halide with an alcohol to form an imino ether and subsequent hydrolysis.
  • a natural penicillin such as Penicillin G or Penicillin V
  • a phosphorus halide to protect the carboxyl group
  • reacting this with an acid halide to form the corresponding penicillin imino halide reacting the imino halide with an alcohol to form an imino ether and subsequent hydrolysis.
  • the present invention provides a novel process for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate of the formula ##STR3## which comprises the steps of (a) contacting a compound of the formula ##STR4## wherein R 1 is C 6 H 5 CH 2 or C 6 H 5 OCH 2 , under anhydrous conditions with a halogenating agent in the presence of a reaction inert organic solvent and an equimolar amount of a tertiary amine at a temperature of from -70° to 20° C. to form an imino halide of formula (III), below, wherein for example, Z is Cl;
  • the invention process has advantages over the prior art methods for providing the coupled amine of formula (I) since the natural penicillin, Penicillin G or Penicillin V, need not be deacylated and the amino group protected prior to coupling with a suitable derivative of penicillanic acid 1,1-dioxide.
  • the natural penicillin need only be converted to a salt, e.g. a sodium salt, and this coupled with e.g., chloromethyl 1,1-dioxopenicillanate to provide the starting compound (II) which is then deacylated by the invention process.
  • halogenating agent as used herein is meant a reagent which readily converts the starting amide of formula (II) to the corresponding imino halide under the instant process conditions without substantial degradation of the starting material or product.
  • halogenating agents are phosphorus pentachloride, phosgene, phosphorus oxychloride, phosphorus oxybromide and oxalyl chloride.
  • a particularly preferred halogenating agent is phosphorus pentachloride.
  • Particularly preferred tertiary amines for the invention process are pyridine and N,N-dimethylaniline.
  • the invention further provides valuable intermediates of the formula ##STR5## wherein R 1 is as previously defined and Z is Cl or OR 2 where R 2 is as previously defined.
  • a particularly preferred value for R 2 is methyl.
  • reaction of a starting compound of formula (II) as defined above with halogenating agent is carried out in the presence of a reaction inert solvent and a tertiary amine.
  • a reaction inert solvent e.g., chloroform, dichloromethane, 1,2-dichloroethane and tetrahydrofuran.
  • Especially preferred solvents are chloroform and dichloromethane.
  • aliphatic, aromatic and aralkyltertiary amines for example, pyridine, triethylamine, ethyl diisopropylamine, N,N-dimethylaniline, N,N-diethylaniline, pyridine, picoline, N-methylmorpholine, etc., will afford satisfactory results, particularly preferred tertiary amines are pyridine and N,N-dimethylaniline.
  • a preferred range of temperature for the first step of the invention process is from about -70° to 20° C. and particularly from about -40° to -20° C.
  • the resulting imino halide intermediate is ordinarily not isolated but for reasons of efficiency the solution containing it is used directly in the next step to form the corresponding imino ether of formula (III) wherein Z is OR 2 and R 2 is as defined above.
  • the conversion of the imino halide to imino ether is carried out by addition of at least an equimolar amount of a primary alcohol, R 2 OH at a temperature of from -70° to 0° C.
  • the imino ether forms in a short time under these conditions, e.g. within from about 10 minutes to 6 hours.
  • the resulting solution of imino ether intermediate is then contacted with water while stirring the reaction mixture for an additional hour or less at a temperature of from -70° to 0° C.
  • the resulting 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate is then isolated by standard methods known to those of skill in the art. For example, the reaction mixture is concentrated, the residue washed with sodium bicarbonate solution to neutralize residual acids and extracted with a water immiscible solvent from which the desired 6-amino compound of formula (I) is obtained by evaporation of the dried extract.
  • the reaction mixture containing the 6-amino compound (I) can be acylated prior to isolation and purification of product.
  • the reaction mixture after the hydrolysis step can be acylated with D(-)-2-phenylglycyl chloride hydrochloride or D(-)-2-(4-hydroxyphenyl)glycyl chloride hydrochloride by methods known in the art to form the corresponding 6-acyl compounds of formula (V) which are useful antibacterial agents.
  • NMR Nuclear magnetic resonance spectra
  • CDCl 3 deuterated chloroform
  • DMSO-d 6 deuterated dimethyl sulfoxide
  • peak positions are reported in parts per million downfield from tetramethylsilane.
  • abbreviations for peak shapes are used: bs, broad singlet; s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet.
  • the resulting hazy solution is concentrated in vacuo to a residual oil.
  • the oil is dissolved in 150 ml ethyl acetate, washed in turn with water (5 ⁇ 80 ml), normal sulfuric acid (3 ⁇ 50 ml), 5% sodium bicarbonate solution (3 ⁇ 50 ml), brine (2 ⁇ 80 ml) and dried (Na 2 SO 4 ).
  • Evaporation of solvent in vacuo gave a residual hard foam, 11 g.
  • the residue is taken up in 7 ml ethyl acetate, 3 ml hexane is added and the solution placed on a silica gel column and eluted with 1:1 ethyl acetate/hexane.
  • the NMR spectrum of the product showed absorptions at 9.4 (d, 1H), 9.0 (broad s, 2H), 7.4 (m, 5H), 5.8 (s, 2H), 5.4 (m, 2H), 5.1 (broad s, 2H), 4.5 (s, 1H), 4.4 (s, 1H), 3.6 (m, 1H), 3.3 (m, 1H), 1.4 (s, 3H) and 1.3 (s, 6H) ppm downfield from tetramethylsilane.
  • the IR spectrum of the product (KBr disc) showed absorptions at 3400, 2950, 1790, 1690, 1320 and 990 cm -1 .
  • the NMR spectrum of the product (DMSO-d 6 /D 2 O) showed absorptions at 7.48 (m, 5H), 5.9 (m, 2H), 5.47 (m, 2H), 5.05 (m, 2H), 4.2 (m, 2H), 3.45 (m, 2H), 1.45 (m, 6H) and 1.36 (m, 6H) ppm downfield from internal tetramethylsilane.
  • the IR spectrum (KBr disc) showed absorptions at 1800-1735 and 1685 cm -1 .

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Cephalosporin Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Cultivation Of Plants (AREA)
US06/438,228 1982-11-01 1982-11-01 Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate Expired - Lifetime US4530792A (en)

Priority Applications (25)

Application Number Priority Date Filing Date Title
US06/438,228 US4530792A (en) 1982-11-01 1982-11-01 Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate
PH29750A PH19573A (en) 1982-11-01 1983-10-21 Process and intermediates for preparation of 1,1-dixopenicillanoyloxymethyl 6-beta aminopenicillanate
EP83306460A EP0108545B1 (en) 1982-11-01 1983-10-25 Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate
AT83306460T ATE24322T1 (de) 1982-11-01 1983-10-25 Verfahren und zwischenprodukte zur herstellung des 1,1-dioxopenicillanoylmethylesters der 6-beta-aminopenicillansaeure.
DE8383306460T DE3368417D1 (en) 1982-11-01 1983-10-25 Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate
CS838030A CS235986B2 (en) 1982-11-01 1983-10-26 Method of 1,1-dioxopenicilanoyloxy-methyl-6-beta-amino- penicilanate production
YU2162/83A YU43989B (en) 1982-11-01 1983-10-28 Process for obtaining 1,1-dioxopenicillanol-oxymethyl-6-beta-amino-penicillanates
FI833961A FI76576C (fi) 1982-11-01 1983-10-28 Foerfarande foer framstaellning av 1,1-dioxopenicillanoyloximetyl-6 -aminopenicillanat.
GT198303898A GT198303898A (es) 1982-11-01 1983-10-28 Procedimiento e intermedios para la preparacion de 1,1-dioxopenicilanoiloximetil 6-beta-aminopenicilanato.
PL1983244352A PL142735B1 (en) 1982-11-01 1983-10-28 Process for preparing penicillanoyloxymethyl-6-beta-aminopenicillinate 1,1-dioxide
CA000440002A CA1204736A (en) 1982-11-01 1983-10-28 Process and intermediates for preparation of 1,1- dioxopenicillan-oyloxymethyl 6-beta- aminopenicillanate
PT77580A PT77580B (en) 1982-11-01 1983-10-28 Process for preparing 1,1-dioxopenicillaoiloxymethyl 6-beta-aminopenicillanate and intermediates thereof
IE2539/83A IE56179B1 (en) 1982-11-01 1983-10-28 Process and intermediates for preparation of 1,1-dioxopenicillan-oyloxymethyl 6-beta-aminopenicillanate
HU833735A HU189769B (en) 1982-11-01 1983-10-31 Process for production of 1,1-dioxo-penicillanoil-6-beta-amino-penicillanate
ZA838091A ZA838091B (en) 1982-11-01 1983-10-31 Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate
ES526942A ES526942A0 (es) 1982-11-01 1983-10-31 Un procedimiento para la preparacion de 6b-aminopenicilanato de 1,1-dioxopenicilanoiloximetilo
AU20821/83A AU541962B2 (en) 1982-11-01 1983-10-31 Process and intermediates for preparation of 1,1- dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate
DD83256136A DD213926A5 (de) 1982-11-01 1983-10-31 Verfahren zur herstellung von 1,1-dioxo-penicillanoyloxymethyl-6-beta-aminopenicillanat
DK497483A DK163515C (da) 1982-11-01 1983-10-31 Fremgangsmaade til fremstilling af 1,1-dioxopenicillanoyloxymethyl-6-beta-aminopenicillanat
GR72828A GR78943B (pl) 1982-11-01 1983-10-31
NZ206108A NZ206108A (en) 1982-11-01 1983-10-31 Process and intermediates for the preparation of a penicillin derivative
IL70095A IL70095A (en) 1982-11-01 1983-10-31 Preparation of 1,1-dioxopenicillanoyl-oxymethyl 6beta-aminopenicillanate
KR1019830005159A KR860001494B1 (ko) 1982-11-01 1983-10-31 1,1-디옥소페니실라노일옥시메틸 6-β-아미노 페니실라네이트의 제조방법
EG681/83A EG15987A (en) 1982-11-01 1983-11-01 Process and intermediates for preparation of 1,1-dioxopenicillan-oyloxymethyl 6-beta-aminopenicillanate
JP58205706A JPS5998090A (ja) 1982-11-01 1983-11-01 １，１−ジオキソペニシラノイロキシメチル−６−ベ−タ−アミノペニシラネ−トの製造法及びその中間体

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US06/438,228 US4530792A (en) 1982-11-01 1982-11-01 Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate

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US4530792A true US4530792A (en) 1985-07-23

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US06/438,228 Expired - Lifetime US4530792A (en) 1982-11-01 1982-11-01 Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate

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US (1) US4530792A (pl)
EP (1) EP0108545B1 (pl)
JP (1) JPS5998090A (pl)
KR (1) KR860001494B1 (pl)
AT (1) ATE24322T1 (pl)
AU (1) AU541962B2 (pl)
CA (1) CA1204736A (pl)
CS (1) CS235986B2 (pl)
DD (1) DD213926A5 (pl)
DE (1) DE3368417D1 (pl)
DK (1) DK163515C (pl)
EG (1) EG15987A (pl)
ES (1) ES526942A0 (pl)
FI (1) FI76576C (pl)
GR (1) GR78943B (pl)
GT (1) GT198303898A (pl)
HU (1) HU189769B (pl)
IE (1) IE56179B1 (pl)
IL (1) IL70095A (pl)
NZ (1) NZ206108A (pl)
PH (1) PH19573A (pl)
PL (1) PL142735B1 (pl)
PT (1) PT77580B (pl)
YU (1) YU43989B (pl)
ZA (1) ZA838091B (pl)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4942229A (en) * 1987-11-25 1990-07-17 Yoshitomi Pharmaceutical Industries, Ltd. Process for the production of penicillanic acid compounds

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2231049A (en) * 1989-04-14 1990-11-07 Yoshitomi Pharmaceutical Method for producing diester compounds
HU212413B (en) * 1990-04-13 1996-06-28 Pfizer Process for producing sultamicillin intermediates

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3896110A (en) * 1971-10-04 1975-07-22 American Home Prod Process for preparation of 6-aminopenicillanic acid
US4234579A (en) * 1977-06-07 1980-11-18 Pfizer Inc. Penicillanic acid 1,1-dioxides as β-lactamase inhibitors
US4244951A (en) * 1979-05-16 1981-01-13 Pfizer Inc. Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide
US4342772A (en) * 1979-02-13 1982-08-03 Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Produktionsaktieselskab) β-Lactam compounds, antibacterial compositions thereof and method of use
US4359472A (en) * 1981-12-22 1982-11-16 Pfizer Inc. Bis-hydroxymethyl carbonate bridged antibacterial agents
US4364957A (en) * 1979-09-26 1982-12-21 Pfizer Inc. Bis-esters of alkanediols as antibacterial agents
US4376076A (en) * 1981-03-23 1983-03-08 Pfizer Inc. Bis-esters of 1,1-alkanediols with 6-beta-hydroxymethylpenicillanic acid 1,1-dioxide

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3929767A (en) * 1971-11-16 1975-12-30 Yamanouchi Pharma Co Ltd Process of producing semi-synthetic penicillin
FR2275460A1 (fr) * 1974-06-20 1976-01-16 Schmoller & Bompard Procede pour la preparation de l'acide 6-aminopenicillanique
US4375434A (en) * 1982-06-21 1983-03-01 Pfizer Inc. Process for 6'-amino-penicillanoyloxymethyl penicillanate 1,1-dioxide

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3896110A (en) * 1971-10-04 1975-07-22 American Home Prod Process for preparation of 6-aminopenicillanic acid
US4234579A (en) * 1977-06-07 1980-11-18 Pfizer Inc. Penicillanic acid 1,1-dioxides as β-lactamase inhibitors
US4342772A (en) * 1979-02-13 1982-08-03 Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Produktionsaktieselskab) β-Lactam compounds, antibacterial compositions thereof and method of use
US4244951A (en) * 1979-05-16 1981-01-13 Pfizer Inc. Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide
US4364957A (en) * 1979-09-26 1982-12-21 Pfizer Inc. Bis-esters of alkanediols as antibacterial agents
US4376076A (en) * 1981-03-23 1983-03-08 Pfizer Inc. Bis-esters of 1,1-alkanediols with 6-beta-hydroxymethylpenicillanic acid 1,1-dioxide
US4359472A (en) * 1981-12-22 1982-11-16 Pfizer Inc. Bis-hydroxymethyl carbonate bridged antibacterial agents

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
B. Baltzer et al., Journal of Antibiotics, 33, 1183 (1980). *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4942229A (en) * 1987-11-25 1990-07-17 Yoshitomi Pharmaceutical Industries, Ltd. Process for the production of penicillanic acid compounds

Also Published As

Publication number Publication date
GR78943B (pl) 1984-10-02
ES8602014A1 (es) 1985-11-01
PH19573A (en) 1986-05-21
KR860001494B1 (ko) 1986-09-27
JPS5998090A (ja) 1984-06-06
YU216283A (en) 1986-02-28
EP0108545B1 (en) 1986-12-17
CS235986B2 (en) 1985-05-15
DE3368417D1 (en) 1987-01-29
DK497483D0 (da) 1983-10-31
ES526942A0 (es) 1985-11-01
PT77580A (en) 1983-11-01
PL244352A1 (en) 1985-02-27
IE56179B1 (en) 1991-05-08
PL142735B1 (en) 1987-11-30
DD213926A5 (de) 1984-09-26
ZA838091B (en) 1985-06-26
AU2082183A (en) 1984-05-10
FI833961A0 (fi) 1983-10-28
NZ206108A (en) 1986-06-11
EG15987A (en) 1989-03-30
ATE24322T1 (de) 1987-01-15
FI76576B (fi) 1988-07-29
JPH0329796B2 (pl) 1991-04-25
IE832539L (en) 1984-05-01
AU541962B2 (en) 1985-01-31
EP0108545A1 (en) 1984-05-16
IL70095A0 (en) 1984-01-31
DK497483A (da) 1984-05-02
IL70095A (en) 1988-03-31
FI833961L (fi) 1984-05-02
PT77580B (en) 1986-05-27
HU189769B (en) 1986-07-28
DK163515C (da) 1992-08-24
KR840007009A (ko) 1984-12-04
YU43989B (en) 1990-02-28
DK163515B (da) 1992-03-09
FI76576C (fi) 1988-11-10
CA1204736A (en) 1986-05-20
GT198303898A (es) 1985-04-20

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